Cellular xenotransplantation of animal cells into people: benefits and risk

The main benefit of xenotransplantation is its potential to overcome the worldwide organ shortage experienced in allotransplantation. Allogeneic transplantation is the only successful therapy for several life-threatening diseases, with cell, tissue or organ donation only partially meeting the demand and many patients dying while waiting for treatment. With supply falling short of demand, it is foreseen that the use of porcine material may at some stage overcome the existing gap between organ availability and clinical need. Recently, pig islet cells have been utilised in clinical trials, with safety being demonstrated. Indeed, pig-derived cells present several advantages: i) porcine cells have a stable function and differentiation pattern and are not tumorigenic; ii) pig cells have been shown to meet the physiological needs in large animal models; iii) the source of pig cells can be scaled up to meet demands in a highly standardised manner, and with respect to animal welfare regulations; iv) ‘designated-pathogen-free’ (DPF) pig lines can be produced, which could result in a higher safety profile than allotransplantation itself; v) the risk of zoonosis, which was raised years ago as the major hurdle, has been recently circumvented and is actually viewed as a controlled risk; and vi) immune risks are being circumvented via the use of genetically modified donor animals and encapsulation of porcine cells, particularly for the treatment of diabetes. Overall, the benefit appears to outweigh potential risks with respect to cellular xenotransplantation and this is discussed further in this review

Search for Intermediate Mass Magnetic Monopoles and Nuclearites with the SLIM experiment

SLIM is a large area experiment (440 m2) installed at the Chacaltaya cosmic ray laboratory since 2001, and about 100 m2 at Koksil, Himalaya, since 2003. It is devoted to the search for intermediate mass magnetic monopoles (107-1013 GeV/c2) and nuclearites in the cosmic radiation using stacks of CR39 and Makrofol nuclear track detectors. In four years of operation it will reach a sensitivity to a flux of about 10-15 cm-2 s-1 sr-1. We present the results of the calibration of CR39 and Makrofol and the analysis of a first sample of the exposed detector.Comment: Presented at the 22nd ICNTS, Barcelona 200

Nomenclature for the C60-Ih and C70-D5h(6) fullerenes (IUPAC Recommendations 2002)

Fullerenes are a new allotrope of carbon characterized by a closed-cage structure consisting of an even number of three-coordinate carbon atoms devoid of hydrogen atoms. This class was originally limited to closed-cage structures with 12 isolated five-membered rings, the rest being six-membered rings. Although it was recognized that existing organic ring nomenclature could be used for these structures, the resulting names would be extremely unwieldy and inconvenient for use. At the same time it was also recognized that established organic nomenclature principles could be used, or adapted, to provide a consistent nomenclature for this unique class of compounds based on the class name fullerene. However, it was necessary to develop an entirely new method for uniquely numbering closed-cage systems. This paper describes IUPAC recommendations for naming and uniquely numbering the two most common fullerenes with isolated pentagons, the icosahedral C60 fullerene and a D5h-C70 fullerene. It also describes recommendations for adapting organic nomenclature principles for naming fullerenes with nonclosed-cage structures, heterofullerenes, derivatives formed by substitution of hydrofullerenes, and the fusion of organic rings or ring systems to the fullerene cage. Finally, this paper suggests methods for describing structures consisting of two or more fullerene units and for denoting configurations of chiral fullerenes and their derivative

Search for strange quark matter and Q-balls with the SLIM experiment

We report on the search for Strange Quark Matter (SQM) and charged Q-balls with the SLIM experiment at the Chacaltaya High Altitude Laboratory (5230 m a.s.l.) from 2001 to 2005. The SLIM experiment was a 427 m$^{2}$ array of Nuclear Track Detectors (NTDs) arranged in modules of $24 \times 24$ cm$^{2}$ area. SLIM NTDs were exposed to the cosmic radiation for 4.22 years after which they were brought back to the Bologna Laboratory where they were etched and analyzed. We estimate the properties and energy losses in matter of nuclearites (large SQM nuggets), strangelets (small charged SQM nuggets) and Q-balls; and discuss their detection with the SLIM experiment. The flux upper limits in the CR of such downgoing particles are at the level of $1.3 10^{-15}$/cm$^{2}$/s/sr (90% CL).Comment: 4 pages, 7 eps figures. Talk given at the 24th International Conference on Nuclear Tracks in Solids, Bologna, Italy, 1-5 September 200

Developing fencing policies in dryland ecosystems

The daily energy requirements of animals are determined by a combination of physical and physiological factors, but food availability may challenge the capacity to meet nutritional needs. Western gorillas (Gorilla gorilla) are an interesting model for investigating this topic because they are folivore-frugivores that adjust their diet and activities to seasonal variation in fruit availability. Observations of one habituated group of western gorillas in Bai-Hokou, Central African Republic (December 2004-December 2005) were used to examine seasonal variation in diet quality and nutritional intake. We tested if during the high fruit season the food consumed by western gorillas was higher in quality (higher in energy, sugar, fat but lower in fibre and antifeedants) than during the low fruit season. Food consumed during the high fruit season was higher in digestible energy, but not any other macronutrients. Second, we investigated whether the gorillas increased their daily intake of carbohydrates, metabolizable energy (KCal/g OM), or other nutrients during the high fruit season. Intake of dry matter, fibers, fat, protein and the majority of minerals and phenols decreased with increased frugivory and there was some indication of seasonal variation in intake of energy (KCal/g OM), tannins, protein/fiber ratio, and iron. Intake of non-structural carbohydrates and sugars was not influenced by fruit availability. Gorillas are probably able to extract large quantities of energy via fermentation since they rely on proteinaceous leaves during the low fruit season. Macronutrients and micronutrients, but not digestible energy, may be limited for them during times of low fruit availability because they are hind-gut fermenters. We discuss the advantages of seasonal frugivores having large dietary breath and flexibility, significant characteristics to consider in the conservation strategies of endangered species

Anti-fibroblast antibodies detected by cell-based ELISA in systemic sclerosis enhance the collagenolytic activity and matrix metalloproteinase-1 production in dermal fibroblasts

Objectives. Antibodies binding to the surface of fibroblasts (anti-fibroblast antibodies: AFA) have been described in systemic sclerosis (SSc). We aimed to assess the effect of AFA on extracellular matrix (ECM) turnover and whether AFA were associated with anti-topoisomerase-I antibody. Methods. IgG were purified from AFA-positive and AFA-negative sera selected within 20 SSc and 20 healthy individuals, and tested on normal dermal fibroblasts, at protein and mRNA level, for their capacity to induce collagen deposition or degradation. Results. Fibroblasts stimulated with AFA-positive but not with AFA-negative and control IgG showed an increased capacity to digest collagen matrix and produce metalloproteinase-1 (MMP-1) while their production of total collagen, type I collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) was unaffected. The steady-state mRNA levels of MMP-1, COL1A1 and TIMP-1 paralleled the protein levels. AFA-positive IgG did not induce Smad 2/3 phosphorylation, indicating that this transforming growth factor-β signalling pathway was not involved. IL-1 and tumour necrosis factor (TNF) neutralization did not reverse the enhanced production of MMP-1, suggesting a direct effect of AFA on fibroblasts. Finally, anti-topoisomerase-I antibodies were present in 11 of 12 AFA-negative IgG, and an anti-topoisomerase-I monoclonal antibody failed to enhance MMP-1 production, thus indicating a lack of correlation between AFA and anti-topoisomerase-I antibody. Conclusions. These results indicate that SSc antibodies binding to fibroblasts enhance matrix degradation and MMP production events that may favour inflammation but do not directly impact on fibrosis developmen

The heterogeneous nature of Fe delivery from melting icebergs

The micronutrient iron (Fe) can be transported from marine terminating glaciers to the ocean by icebergs. There are however few observations of iceberg Fe content, and the flux of Fe from icebergs to the offshore surface ocean is poorly constrained. Here we report the dissolved Fe (DFe), total dissolvable Fe (TdFe) and ascorbic acid extractable Fe (FeAsc) sediment content of icebergs from Kongsfjorden, Svalbard. The concentrations of DFe (range 0.63 nM – 536 nM, mean 37 nM, median 6.5 nM) and TdFe (range 46 nM – 57 µM, mean 3.6 µM, median 144 nM) both demonstrated highly heterogeneous distributions and there was no significant correlation between these two fractions. FeAsc (range 0.0042 to 0.12 wt. %) was low compared to both previous measurements in Kongsfjorden and to current estimates of the global mean. FeAsc content per volume ice did however, as expected, show a significant relationship with sediment loading (which ranged from < 0.1 – 234 g L-1 of meltwater). In the Arctic, icebergs lose their sediment load faster than ice volume due to the rapid loss of basal ice after calving. We therefore suggest that the loss of basal ice is a potent mechanism for the reduction of mean TdFe and FeAsc per volume of iceberg. Delivery of TdFe and FeAsc to the ocean is thereby biased towards coastal waters where, in Kongsfjorden, DFe (18 ± 17 nM) and TdFe (mean 8.1 µM, median 3.7 µM) concentrations were already elevated

Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy

Background: Despite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6), D-dimer, and high-sensitivity C-reactive protein (hsCRP) levels with serious non-AIDS conditions or death in 3 large cohorts. Methods: In HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR) adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability) were used to predict risk reductions in serious non-AIDS conditions or death associated with lower “usual” levels of IL-6 and D-dimer. Results: Over 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63), 1.28 (95% CI: 1.14 to 1.44), and 1.17 (95% CI: 1.09 to 1.26) per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower “usual” IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46%) in the risk of serious non-AIDS conditions or death if the relationship is causal. Conclusions: Both IL-6 and D-dimer are independently associated with serious non-AIDS conditions or death among HIV-positive adults with suppressed virus. This suggests that treatments that reduce IL-6 and D-dimer levels might substantially decrease morbidity and mortality in patients on suppressive ART. Clinical trials are needed to test this hypothesis